Measuring physical properties of neuronal and glial cells with resonant microsensors.

Abstract

Microelectromechanical systems (MEMS) resonant sensors provide a high degree of accuracy for measuring the physical properties of chemical and biological samples. These sensors enable the investigation of cellular mass and growth, though previous sensor designs have been limited to the study of homogeneous cell populations. Population heterogeneity, as is generally encountered in primary cultures, reduces measurement yield and limits the efficacy of sensor mass measurements. This paper presents a MEMS resonant pedestal sensor array fabricated over through-wafer pores compatible with vertical flow fields to increase measurement versatility (e.g., fluidic manipulation and throughput) and allow for the measurement of heterogeneous cell populations. Overall, the improved sensor increases capture by 100% at a flow rate of 2 μL/min, as characterized through microbead experiments, while maintaining measurement accuracy. Cell mass measurements of primary mouse hippocampal neurons in vitro, in the range of 0.1–0.9 ng, demonstrate the ability to investigate neuronal mass and changes in mass over time. Using an independent measurement of cell volume, we find cell density to be approximately 1.15 g/mL.